It has been hypothesized that the pathogenesis of bronchial asthma might be due, in part, to a disruption in either the autonomic nervous system, the sympathetic nervous system, or in the beta receptor-adenylate cyclase inter-relationship. The objective of this proposal is to investigate the beta adrenergic-adenylate cyclase system using healthy, sensitized, and anaphylactic guinea pig lungs and rat mast cells as models of healthy individuals, asthmatics in remission, and asthmatics undergoing an attack. The parameters that will be measured are: (a) The number of functional binding sites; (b) The dissociation constants of several receptor agonists; (c) The basal and hormone stimulated adenylate cyclase activities; and (d) The membrane phospholipid and fatty acid composition. These parameters will be determined under control conditions and after the lungs have been treated (a) To produce super or subsensitivity of the receptor; (b) With phospholipase A2; or (c) With guanylyl-imidodiphosphate. It is hoped that the parameters will establish whether or not the disruption is inherent in the receptor, related to the receptor-enzyme coupling, in the cyclase per se, or not associated with this system. By comparing the treated samples (nonsensitized) with the non-treated sensitized samples, it will be possible to determine if the states produced by any of the treatments mimic that of the sensitized lung (and assuming the model is a good approximation, the asthmatic in remission). The binding and dissociation measurements will be determined by the method of Mukherjee et al. (1975a) using (-)3H dihydroalprenolol. The phospholipid and fatty acid analyses will be carried out according to methods of Rooney et al. (1974). Adenylate cyclase activity will be determined using alpha-32P-ATP and a creatine phosphate-creating kinase regenerating system.